High-Glucose Conditions Promote Anchorage-Independent Colony Growth in Human Breast Cancer MCF-7 Cells.

Previous studies have shown that hyperglycemia is connected to the malignant progression of breast cancer; however, the effects of hyperglycemia on tumorigenic potential in breast cancer cells are largely unknown. Here, we demonstrated that the ability of the human breast cancer cell line MCF-7 to undertake anchorage-independent colony growth was significantly enhanced when cultured under high-glucose conditions compared with that under physiological glucose conditions. The high-glucose conditions also promoted phosphorylation of Akt, suggesting that MCF-7 cells cultured in these conditions acquired an increased ability to undergo anchorage-independent growth at least in part through Akt activation, which has been linked to the development of breast cancer. These results raise the possibility that regulation of Akt activity contributes to the tumorigenesis of breast cancer under high-glucose conditions, and we propose that additional analyses of high glucose-induced tumor formation would provide novel strategies for the diagnosis and therapy of breast cancer with hyperglycemia.

Potential Roles of GLUT12 for Glucose Sensing and Cellular Migration in MCF-7 Human Breast Cancer Cells Under High Glucose Conditions.

BACKGROUND/AIM: Recent reports have indicated that hyperglycaemia is associated with breast cancer progression. High glucose conditions corresponding to hyperglycaemia significantly promote migration of MCF-7 human breast cancer cells, however, little is known about the mechanisms of glucose sensing for the acquisition of migratory properties by MCF-7 cells. This study investigated glucose sensing and mediation, which are responsible for the high motility of MCF-7 cells. MATERIALS AND METHODS: We evaluated the migration of MCF-7 cells cultured in high glucose-containing medium and essential regulatory factors from the perspective of the glucose transport system. RESULTS: We demonstrated that glucose transporter 12 (GLUT12) protein level increased in MCF-7 cells and co-localized with actin organization under high glucose conditions. Moreover, GLUT12-knockdown completely abrogated high glucose-induced migration, indicating that GLUT12 functionally participates in sensing high glucose concentrations. CONCLUSION: GLUT12 plays a critical role in the model of breast cancer progression through high glucose concentrations.

High glucose level promotes migration behavior of breast cancer cells through zinc and its transporters.

BACKGROUND: The diabetes patients have been associated with an increased risk of mortality by breast cancer and there are difference between the breast cancer patients with diabetes, and their nondiabetic counterparts in the regimen choice and effects of breast cancer treatment. However, the pathophysiological relationships of diabetes and breast cancer have not yet been elucidated in detail. In this study, we investigate the breast cancer cell line, MCF-7 motility, which linked to invasion and metastasis, in high glucose level corresponding to hyperglycemia and the role of Zn and its transporter. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated the significant motility of MCF-7 cultured in hyperglycemic level (25 mM glucose) in comparison to normal physiological glucose level (5.5 mM glucose). The other hand, the osmotic control medium, 5.5 mM glucose with 19.5 mM mannitol or fructose had no effect on migratory, suggesting that high glucose level promotes the migration of MCF-7. Moreover, the activity of intracellular Zn(2+) uptake significantly increased in high glucose-treated cells in comparison to 5.5 mM glucose, and the mRNA expression of zinc transporters, ZIP6 and ZIP10, was upregulated in 25 mM glucose-treated cells. The deficiency of ZIP6 or ZIP10 and intracellular Zn(2+) significantly inhibited the high migration activity in 25 mM glucose medium, indicating that Zn(2+) transported via ZIP6 and ZIP10 play an essential role in the promotion of cell motility by high glucose stimulation. CONCLUSION/SIGNIFICANCE: Zinc and its transporters, ZIP6 and ZIP10, are required for the motility stimulated with high glucose level. These findings provide the first evidence proposing the novel strategies for the diagnosis and therapy of breast cancer with hyperglycemia.

CD44 is critical for airway accumulation of antigen-specific Th2, but not Th1, cells induced by antigen challenge in mice.

CD44 is a cell adhesion molecule involved in lymphocyte infiltration of inflamed tissues. We previously demonstrated that CD44 plays an important role in the development of airway inflammation in a murine model of allergic asthma. In this study, we investigated the role of CD44 expressed on CD4(+) T cells in the accumulation of T-helper type 2 (Th2) cells in the airway using CD44-deficient mice and anti-CD44 monoclonal antibodies. Antigen-induced Th2-mediated airway inflammation and airway hyperresponsiveness (AHR) in sensitized mice were reduced by CD44-deficiency. These asthmatic responses induced by the transfer of antigen-sensitized splenic CD4(+) T cells from CD44-deficient mice were weaker than those from WT mice. Lack of CD44 failed to induce AHR by antigen challenge. Expression level and hyaluronic acid receptor activity of CD44, as well as Neu1 sialidase expression on antigen-specific Th2 cells, were higher than those on antigen-specific Th1 cells. Anti-CD44 antibody preferentially suppressed the accumulation of those Th2 cells in the airway induced by antigen challenge. Our findings indicate that CD44 expressed on CD4(+) T cells plays a critical role in the accumulation of antigen-specific Th2 cells, but not Th1 cells, in the airway and in the development of AHR induced by antigen challenge.

Accommodation and convergence palsy caused by lesions in the bilateral rostral superior colliculus.

PURPOSE: To report a patient who developed accommodation and convergence palsy caused by lesions in the bilateral rostral superior colliculus. DESIGN: Observational case report. METHODS: A 30-year-old right-handed man experienced sudden onset of diplopia and blurred vision at near vision. RESULTS: The patient showed accommodation and convergence palsy. Magnetic resonance imaging revealed lesions located in the bilateral rostral superior colliculus. CONCLUSION: These findings suggest that the rostral superior colliculus is involved in the control of accommodation and vergence eye movements.